Microphysiological System to Explore Anti-Cancer Therapies and PK/PD Relationships

The dynamic and complex crosstalk between target cells and their microenvironment modulates physiological functions, pathological processes, and response to therapy. This crosstalk is mediated by direct cell-cell contact and indirect interactions via secreted soluble mediators, extracellular membrane components and modulators, extracellular vesicles. The difficulties in recapitulating these heterogeneous microenvironments with human cell models, with mature cell functionality and without the confounding effects of heterologous extracellular matrices, are a bottleneck in deciphering the crosstalk mechanisms and predicting their effect on therapeutic efficacy. To overcome these limitations, our team develops 3D cell models of disease, applying advanced cell culture approaches (3D culture, co-culture, cell immobilization) and systems (perfusion, bioreactors) to human pluripotent stem cells, other patient-derived cells, and human cell lines. By integrating cell biology, biochemical, imaging, transcriptomics, and proteomics approaches, we can depict the dynamic modulation of a specific cell microenvironment over time or in response to a therapeutic challenge. Recent advances in innate immune-competent 3D cell models of the central nervous system and carcinomas, and their application in the recapitulation of pathological disease features and utility to address the influence of the immune microenvironment in response to advanced therapeutics, such as gene therapy vectors and biologicals.